Coverage of intermittent preventive treatment of malaria in infants after four years of implementation in Sierra Leone.

BACKGROUND: Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. METHODS: A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. RESULTS: A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. CONCLUSION: In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

Efficacy of artemisinin-based combination therapies and prevalence of molecular markers associated with artemisinin, piperaquine and sulfadoxine-pyrimethamine resistance in Sierra Leone.

Currently, the national malaria control programme (NMCP) of Sierra Leone recommends artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) as first- and second-line treatment for uncomplicated malaria, respectively, and artesunate + sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment during pregnancy and for infants. In 2016, the NMCP conducted a study to assess the clinical and parasitological responses of children under five years to ASAQ, AL and dihydroartemisinin-piperaquine (DHA/PPQ) according to the WHO protocol. Day-0 samples were tested for mutations in the Kelch 13 gene (pfk13) and dihydrofolate reductase/dihydropteroate synthase (pfdhfr/pfdhps) genes associated with artemisinin and SP resistance, respectively, and amplification in the pfplasmepsin2 gene for piperaquine resistance. A total of 295 (ASAQ = 128, AL = 64 and DHA/PPQ = 103) eligible children were enrolled at three sites. PCR-corrected 100% adequate clinical and parasitological response and no parasitaemia on day-3 were observed for all patients in each treatment group. Of the 278 samples with interpretable molecular data, only 2.2% carried non-synonymous pfk13 mutants (A578S, I646T), which are not associated with artemisinin resistance. None of the 103 day-0 samples from the DAH/PPQ group had pfplasmepsin2 gene amplification, confirming the absence of piperaquine resistance. The prevalence of the triple pfdhfr mutant (N51I/C59R/S108N) was close to or reached fixation (97.4-100%). For combined pfdhfr/pfdhps mutation, 55-71% carried the quadruple (N51I/C59R/S108N+A437G) mutant and about 10% the quintuple mutant N51I/C59R/S108N+A437G/K540E. Our findings confirm that ASAQ, AL and DHA/PPQ were highly effective for the treatment of uncomplicated malaria in the study areas, and neither pfk13 validated mutations nor pfplasmepsin2 multiple copies were found. The very low prevalence of the quintuple mutant in this study supports the NMCP's decision to introduce intermittent preventive treatment for infants with SP in the districts with high malaria transmission.

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone.

BACKGROUND: As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate-amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014-January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. METHODS: The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. RESULTS: After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38-48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41-52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32-38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39-52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29-38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13-46 %) at week 1 post-first MDA and much lower during all the weeks post-second MDA. CONCLUSIONS: The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.